microRNAs (miRNAs) are important regulators of cellular homeostasis and exert their effect by directly controlling protein expression. We have previously reported an age-dependent negative association between microRNA-99b (miR-99b-5p) expression and muscle protein synthesis in human muscle in vivo. Here we investigated the role of miR-99b-5p as a potential negative regulator of protein synthesis via inhibition of mammalian target for rapamycin (MTOR) signaling in human primary myocytes. Overexpressing miR-99b-5p in human primary myotubes from young and old subjects significantly decreased protein synthesis with no effect of donor age. A binding interaction between miR-99b-5p and its putative binding site within the MTOR 3′-untranslated region (UTR) was confirmed in C₂C₁₂ myoblasts. The observed decline in protein synthesis was, however, not associated with a suppression of the MTOR protein but of its regulatory associated protein of mTOR complex 1 (RPTOR). These results demonstrate that modulating the expression levels of a miRNA can regulate protein synthesis in human muscle cells and provide a potential mechanism for muscle wasting in vivo.

中文翻译：

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MicroRNA-99b-5p下调人类原代肌管中的蛋白质合成。

microRNA（miRNA）是细胞稳态的重要调节剂，可通过直接控制蛋白质表达发挥其作用。我们以前已经报道了体内人类肌肉中microRNA-99b（miR-99b-5p）表达与肌肉蛋白合成之间的年龄依赖性负相关。在这里，我们研究了miR-99b-5p通过抑制哺乳动物对雷帕霉素（MTOR）信号传导的靶标在人类原代心肌细胞中作为潜在的蛋白质合成负调节剂的作用。来自年轻和老年受试者的人类原代肌管中过表达的miR-99b-5p显着降低了蛋白质合成，而没有供体年龄的影响。在C ₂ C _12中证实了miR-99b-5p及其在MTOR 3'非翻译区（UTR）内的假定结合位点之间的结合相互作用。成肌细胞。但是，观察到的蛋白质合成下降与抑制MTOR蛋白质无关，而与mTOR复合物1（RPTOR）的调控相关蛋白质无关。这些结果表明，调节miRNA的表达水平可以调节人肌肉细胞中的蛋白质合成，并提供体内肌肉消瘦的潜在机制。